Hotspots of Mammalian Chromosome Evolution


The emergence of high‐quality mammalian whole genome sequence data has enabled for the first time a comprehensive investigation of the molecular mechanisms of mammalian chromosome evolution. New sequence data reveal an unexpected degree of chromosomal plasticity, both in the healthy human population and in cross‐species evolutionary comparisons. In the context of the evolutionary framework established by comparative cytogenetics, the new data reveal lineage‐specific chromosomal rearrangement pattern often linked to particular duplicated or repetitive sequences. Multispecies comparisons indicate evolutionary reuse of certain chromosomal breakpoints as well as some associations of breakpoints to cytogenetic chromosomal landmarks.

Keywords: genome plasticity; segmental duplications; karyotype evolution; chromosome rearrangement mechanisms; comparative genetics

Figure 1.

Chromosomal homologies to human chromosome 1 detected by reciprocal Zoo‐FISH and genome sequence alignments delineating a region of high‐evolutionary plasticity around band 1q22. The picture shows a GTG‐banded ideogram of human chromosome 1 on the left. The vertical bars to the right of the ideogram depict the extent of the chromosomal orthologies in 11 eutherian species. Zoo‐FISH data are given in saturated colours and genome sequence‐based orthologies are indicated by lighter coloured bars. Please note the clustering of breakpoints around chromosome band 1q22 (indicated by the green frame) as described in greater detail by Murphy et al.. The genome sequence alignment data are taken from the ENSEMBL genome browser (

Figure 2.

Mechanisms causing chromosomal rearrangements and examples of selection mechanisms directing chromosomal evolution in germline cells. The diagram indicates at which points of the simplified germline cell life cycle the mechanisms are likely to act. The boxes A, B, C and D indicate potential DNA damage causes and DNA repair mechanisms generating chromosomal rearrangements. The position of selection mechanisms is given by the lowercase letters: (a) cell cycle arrest caused by nondisjunction of rearranged chromosomes; rescue through neocentromere formation, cascading chromosome rearrangements through breakage‐fusion‐bridge cycles, (b) meiotic drive, induction of additional chromosomal imbalances by crossing‐over between rearrangement heterozygotes; meiotic arrest due to transcriptional silencing of unpaired chromatin, (c) selection against genetic imbalances through competition among gametes in folliculogenesis and sperm motility, (d) selection against genetic imbalances ; selection against disturbances of the 3D nuclear architecture and (e) selection due to infertility or subfertility caused by meiotic segregation problems.



Armengol L, Pujana MA, Cheung J et al. (2003) Enrichment of segmental duplications in regions of breaks of synteny between the human and mouse genomes suggest their involvement in evolutionary rearrangements. Human Molecular Genetics 12: 2201–2208.

Bailey JA, Baertsch R, Kent WJ et al. (2004) Hotspots of mammalian chromosomal evolution. Genome Biology 5: R23.

Bauchinger M and Götz G (1979) Distribution of radiation induced lesions in human chromosomes and dose‐effect relation analysed with G‐banding. Radiation Environmental Biophysics 16: 355–366.

Camats N, Ruiz‐Herrera A, Parrilla JJ et al. (2006) Genomic instability in rat: breakpoints induced by ionising radiation and interstitial telomeric‐like sequences. Mutation Research 595: 156–166.

Carbone L, Vessere GM, ten Hallers BF et al. (2006) A high‐resolution map of synteny disruptions in gibbon and human genomes. PLoS Genetics 2: e223.

Ferguson‐Smith MA and Trifonov V (2007) Mammalian karyotype evolution. Nature Reviews. Genetics 8: 950–962.

Fioretos T (2006) Mechanisms underlying neoplasia‐associated genomic rearrangements. In: Lupski JR and Pawel Stankiewicz (eds) Genomic Disorders – The Genomic Basis of Disease, pp. 327–339. Totowa, NJ: Humana Press.

Froenicke L (2005) Origins of primate chromosomes – as delineated by Zoo‐FISH and alignments of human and mouse draft genome sequences. Cytogenetic and Genome Research 108: 122–138.

Froenicke L, Caldes MG, Graphodatsky A et al. (2006) Are molecular cytogenetics and bioinformatics suggesting diverging models of ancestral mammalian genomes? Genome Research 16: 306–310.

Hartmann N and Scherthan H (2004) Characterization of ancestral chromosome fusion points in the Indian muntjac deer. Chromosoma 112: 213–220.

Huang L, Wang J, Nie W et al. (2006) Tandem chromosome fusions in karyotypic evolution of Muntiacus: evidence from M. feae and M. gongshanensis. Chromosome Research 14: 637–647.

Hurles ME and Lupski JR (2006) Recombination hotspots in nonallelic homologous recombination. In: Lupski JR and Pawel Stankiewicz (eds) Genomic Disorders – The Genomic Basis of Disease, pp. 341–355. Totowa, NJ: Humana Press.

Jiang Z, Tang H, Ventura M et al. (2007) Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nature Genetics 39: 1361–1368.

Johnson ME, Cheng Z, Morrison VA et al. (2006) Recurrent duplication‐driven transposition of DNA during hominoid evolution. Proceedings of the National Academy of Sciences of the USA 103: 17626–17631.

Kohn M, Hogel J, Vogel W et al. (2006) Reconstruction of a 450‐My‐old ancestral vertebrate protokaryotype. Trends in Genetics 22: 203–210.

Korbel JO, Urban AE, Grubert F et al. (2007) Systematic prediction and validation of breakpoints associated with copy‐number variants in the human genome. Proceedings of the National Academy of Sciences of the USA 104: 10110–10115.

Ma J, Zhang L, Suh BB et al. (2006) Reconstructing contiguous regions of an ancestral genome. Genome Research 16: 1557–1565.

Mehan MR, Almonte M, Slaten E et al. (2007) Analysis of segmental duplications reveals a distinct pattern of continuation‐of‐synteny between human and mouse genomes. Human Genetics 121: 93–100.

Metcalfe CJ, Bulazel KV, Ferreri GC et al. (2007) Genomic instability within centromeres of interspecific marsupial hybrids. Genetics 177: 2507–2517.

Mikkelsen TS, Wakefield MJ, Aken B et al. (2007) Genome of the marsupial Monodelphis domestica reveals innovation in non‐coding sequences. Nature 447: 167–177.

Murphy WJ, Fronicke L, O'Brien SJ et al. (2003) The origin of human chromosome 1 and its homologs in placental mammals. Genome Research 13: 1880–1888.

Murphy WJ, Larkin DM, Everts‐van der Wind A et al. (2005) Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps. Science 309: 613–617.

Nadeau JH and Taylor BA (1984) Lengths of chromosomal segments conserved since divergence of man and mouse. Proceedings of the National Academy of Sciences of the USA 81: 814–818.

Natarajan AT, Balajee AS, Boei JJ et al. (1996) Mechanisms of induction of chromosomal aberrations and their detection by fluorescence in situ hybridization. Mutation Research 372: 247–258.

Pardo‐Manuel de Villena F and Sapienza C (2001) Female meiosis drives karyotypic evolution in mammals. Genetics 159: 1179–1189.

Peng Q, Pevzner PA and Tesler G (2006) The fragile breakage versus random breakage models of chromosome evolution. PLoS Computational Biology 2: e14.

Pevzner P and Tesler G (2003) Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution. Proceedings of the National Academy of Sciences of the USA 100: 7672–7677.

Ruiz‐Herrera A, Castresana J and Robinson TJ (2006) Is mammalian chromosomal evolution driven by regions of genome fragility? Genome Biology 7: R115.

Ruiz‐Herrera A, Garcia F, Azzalin C et al. (2002) Distribution of intrachromosomal telomeric sequences (ITS) on Macaca fascicularis (primates) chromosomes and their implication for chromosome evolution. Human Genetics 110: 578–586.

Ruiz‐Herrera A and Robinson TJ (2007) Chromosomal instability in Afrotheria: fragile sites, evolutionary breakpoints and phylogenetic inference from genome sequence assemblies. BMC Evolutionary Biology 7: 199.

Schwartz M, Zlotorynski E and Kerem B (2006) The molecular basis of common and rare fragile sites. Cancer Letters 232: 13–26.

Sharp AJ and Eichler EE (2006) Segmental duplications. In: Lupski JR and Pawel Stankiewicz (eds) Genomic Disorders – The Genomic Basis of Disease, pp. 73–87. Totowa, NJ: Humana Press.

Spiteri E, Babcock M, Kashork CD et al. (2003) Frequent translocations occur between low copy repeats on chromosome 22q11.2 (LCR22 s) and telomeric bands of partner chromosomes. Human Molecular Genetics 12: 1823–1837.

Stankiewicz P, Shaw CJ, Dapper JD et al. (2003) Genome architecture catalyzes nonrecurrent chromosomal rearrangements. American Journal of Human Genetics 72: 1101–1116.

Svartman M, Stone G, Page JE et al. (2004) A chromosome painting test of the basal Eutherian karyotype. Chromosome Research 12: 45–53.

Ventura M, Weigl S, Carbone L et al. (2004) Recurrent sites for new centromere seeding. Genome Research 14: 1696–1703.

Webber C and Ponting CP (2005) Hotspots of mutation and breakage in dog and human chromosomes. Genome Research 15: 1787–1797.

Wienberg J (2004) The evolution of eutherian chromosomes. Current Opinion in Genetics & Development 14: 657–666.

Wilson AC, Bush GL, Case SM et al. (1975) Social structuring of mammalian populations and rate of chromosomal evolution. Proceedings of the National Academy of Sciences of the USA 72: 5061–5065.

Further Reading

Lupski JR and Stankiewicz P (eds) (2006) Genomic Disorders – The Genomic Basis of Disease. Totowa, NJ: Humana Press.

Muller S (2006) Primate chromosome evolution. In: Lupski JR and Stankiewicz P (eds) Genomic Disorders – The Genomic Basis of Disease, pp. 133–152. Totowa, NJ: Humana Press.

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Froenicke, Lutz, and Lyons, Leslie A(Jul 2008) Hotspots of Mammalian Chromosome Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020750]